Drug use rates vary significantly among different populations such as household members, students and arrestees, and the accuracy of self- reports of drug use may be questionable. Drug testing of biological specimens such as urine, saliva, sweat and hair provides an objective means of diagnosis of drug use and monitoring subjects while in treatment. Traditionally, urine testing has been used in the past, but this technology has limitations. In a series of ongoing studies, a variety of alternative biological fluids and tissues are being evaluated for their usefulness in monitoring individual patterns of substance abuse. Clinical studies were designed to determine the identity, concentration, time course, dose dependency and variability of drug and metabolite excretion in urine, plasma, saliva, sweat, skin, sebum, and hair following administration of single doses of drugs of abuse to human subjects. Each biological specimen appears to be unique and offers a somewhat different pattern of information regarding drug use over time. For example, hair testing offers the possibility of detecting drug use that could have occurred within a period of several months and could be useful in monitoring individuals in long-term treatment programs and in prevalence studies. In contrast, saliva testing is a short term measure of drug exposure that might correlate closely with drug levels in blood and with drug-induced effects. Sweat testing can be used for drug monitoring over a period of 1-2 weeks. Each matrix may be useful for drug testing in different settings. However, there may also be disadvantages associated with the use of a particular biological matrix. The risk of false positives arising from environmental drug contamination is being evaluated along with the possibility of ethnic bias in testing. Basic pharmacological properties such as dose-concentration and concentration-time relationship are evaluated. Overall, each biological matrix shows promise of revealing useful information regarding an individual's drug exposure history.